Biology subjects

Artyomov, M.

Publications and source records attributed to Artyomov, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Cysteine reduction rather than methionine restriction promotes immunometabolic fitness to confer survival benefit in aging

Elevated sulfur-containing amino acids (SAA; methionine and cystine) are linked to human mortality. While methionine restriction (MR) extends lifespan in animals, it is often ignored that traditional longevity-promoting MR diets also lack cystine. When dietary cystine is eliminated, host redirects substrates from methionine cycle and generates cysteine via cystathionine {gamma}-lyase (CTH) in transsulfuration pathway, leaving it unclear which SAA controls aging. Here, we show that selective cysteine restriction in Caenorhabditis elegans enhanced lifespan and stress survival independently of methionine. Notably, cysteine-free diets (methionine-replete or restricted) in Cth-deficient mice induced pro-metabolic effects, whereas MR with normal cysteine was ineffective. Sustained 70% cysteine reduction in aged Cth-/- mice reprogrammed the immunometabolic axis, conferring healthspan benefits. Thus, lowering cysteine while keeping the methionine pool intact enhances healthy lifespan.

physiology↗

bioRxiv2026

Immune Checkpoint Therapy Drives Maturation of a Cellular Neighborhood Nucleated by T Cell-APC Triads Enabling Spatially Compartmentalized Tumor Immunity

Spatially organized immune hubs of T cells and antigen-presenting cells (APCs) have been linked to immune checkpoint therapy (ICT) efficacy, yet the mechanisms underlying their function remain unclear. Using CODEX multiplex imaging, we longitudinally characterized the dynamic evolution of intratumoral cellular neighborhoods (CN) defined by "triad" interactions of CD4 and CD8 T cells with two distinct myeloid APC populations: cDC1s and IFN{gamma}-activated macrophages. We termed this CN the immunity-promoting CN (IP-CN) and tracked its progressive development during tumor rejection induced by -CTLA-4/-PD-1 therapy. A coordinated IFN{gamma} and TNF signaling signature accompanied the IP-CN assembly. Over time, the IP-CN underwent functional maturation, forming specialized sub-neighborhoods that compartmentalized proliferating T cells at the tumor periphery versus cytotoxic T effector cells interacting with tumor cell targets. Our findings reveal a spatiotemporal mechanism by which the IP-CN sustains and amplifies cytotoxic T cell responses, demonstrating how T cell-APC neighborhoods orchestrate tumor immunity.

immunology↗

bioRxiv2026

CD8+ T cells are primed by cDC1 and exacerbate tau-mediated neurodegeneration

There are changes in adaptive immunity in Alzheimers disease (AD) and increases in activated CD8+ T cells in brain correlate with tau pathology1-3. However, which cells mediate T cell priming in tau-mediated neurodegeneration remains unclear. In different conditions such as cancer, viral infections, and autoimmune diseases outside the CNS, conventional type-1 dendritic cells (cDC1) perform antigen cross-presentation to prime CD8+ T cells4,5. We demonstrate that tauopathy mice deficient in cDC1 are markedly protected against tau-mediated neurodegeneration and display a selective decrease in brain CD8+ T cell infiltration and glial reactivity. The remaining CD8+ T cells showed an antigen inexperienced status with less clonal expansion, indicating suboptimal T cell priming. We confirm that brain derived antigens are presented in secondary lymphoid tissues to prime CD8+ T cells. Our study identifies cDC1 cells as critical for CD8+ T cell priming outside the CNS. This priming is required for a large increase of activated CD8+ T cells in the brain which promotes tau-mediated neurodegeneration.

neuroscience↗

bioRxiv2025

Myofibroblastic CAFs arising from bone-resident osteoblast precursors retain an osteolineage signature and support breast cancer progression via Osterix-mediated signaling.

Cancer-associated fibroblasts (CAFs) are a major component of the breast cancer (BC) microenvironment, involved in tumor progression and resistance to therapy. Despite the recent identification of multiple CAF subtypes with unique functions, it remains unclear whether each subtype arises from a distinct precursor or a shared common progenitor. Here, we identified a unique subpopulation of myofibroblast CAFs (myCAFs) arising from committed Osterix (Osx)+ osteoblast progenitors in the bone, recruited to primary tumors in both murine BC models and BC patients. Osx+myCAFs exhibit strong protumorigenic features and retain osteoblastic gene expression, which distinguishes them from OsxnegCAF subsets. Osx drives the expression of extracellular matrix remodeling genes and promotes tumor growth via the secretion of MMP13, a key Osx target gene. Finally, we find that increased Osx+myCAFs and a stromal osteolineage gene signature correlate with poor therapeutic response and reduced BC patient survival.

cancer biology↗

bioRxiv2025

The Nox2 NADPH oxidase regulates neutrophilic inflammation in the oral cavity

The leukocyte NADPH oxidase 2 (NOX2) is an important regulator of inflammatory responses, independent of its antimicrobial activity. Inactivating mutations in NOX2 cause chronic granulomatous disease (CGD), a severe immunodeficiency associated with recurrent infections and dysregulated neutrophilic inflammation. Recurrent oral ulcers, stomatitis, gingivitis, and other inflammatory issues affecting the oral mucosa have been observed in patients with CGD; however, the underlying mechanisms are not known. Here, we present evidence that the extensive inflammatory destruction of oral mucosal tissues observed in Nox2-deficient or CybbKOmice was not caused by impaired antimicrobial surveillance against oral pathobionts but instead resulted from a cell-intrinsic dysregulation of neutrophil inflammatory responses. Transcriptional and cellular profiling of oral tissues isolated from wild-type and CybbKO mice showed a dominant neutrophil signature, which was accompanied by a significant upregulation of several bone-resorbing, tissue-degrading inflammatory cytokines and a reduced expression of nuclear factor erythroid 2-related factor 2 (Nrf2) regulated genes. Mechanistically, hyperinflammatory responses were mitigated by restoring Nrf2 transcriptional activity using a synthetic agonist. Thus, our studies show that Nox2 oxidase and its derived reactive oxygen species are crucial for balanced recruitment and cell-intrinsic regulation of neutrophil inflammatory responses within oral tissues in an Nrf2-dependent manner.

immunology↗

bioRxiv2025

Virion stripping: A new role for bacterial proteases

We demonstrate that proteases produced by the oro-pharyngeal bacterial colonizer Porphyromonas gingivalis (Pg) reduce viral burden and modulate host interferon responses during respiratory syncytial virus (RSV) infection. Several oral bacteria, including Pg, have been shown to translocate to the upper airways through sub-clinical micro-aspiration. Our findings reveal that Pg, upon translocating to this new niche, significantly attenuated lung damage by reducing viral loads during respiratory viral infections in the lungs of wild-type mice. This protective effect was attributed to the activity of gingipains, cysteine endopeptidases produced by Pg, which cleaved envelope glycoproteins on RSV as well as on related murine-specific Sendai virus (SeV), thereby impairing their infectious capacity. Notably, the reduction in viral loads was independent of interferon lambda (IFN-{lambda}) signaling, which is actively suppressed by Pg in airway epithelial cells. However, the complete absence of IFN-{lambda} signaling resulted in a stronger inflammatory response despite a low viral load. Thus, we show a previously undescribed role for the oro-respiratory bacterial colonizer Pg in creating bottlenecks to viral infection by the activity of its proteases. SIGNIFICANCE STATEMENTReciprocal interactions between microbial colonizers and host epithelial cells are critical for providing initial defense against viral infections. However, our understanding of this phenomenon has been limited to microbiota-derived ligands that activate host pattern recognition receptors (PRRs), inducing basal interferon expression and downstream antiviral genes. Here, we present a novel mechanism that relies on microbial proteases to directly reduce viral load. Specifically, we discovered that the infectious capacity of the Respiratory Syncytial Virus (RSV) was significantly inhibited upon contact with the proteases (gingipains) produced by the oropharyngeal colonizer Porphyromonas gingivalis. Gingipains caused proteolytic degradation of the RSV envelope and attachment proteins, rendering them inactive. This preemptive reduction in viral infectious capacity consequently diminished the severity of respiratory viral infections in an IFN-independent manner.

microbiology↗

bioRxiv2024

Non-negative matrix factorization and deconvolution as dual simplex problem

Non-negative matrix factorization (NMF) is one of the most powerful linear algebra tools, which has found application in various areas of data analysis, including computational biology. Despite numerous optimization methods devised for NMF, our comprehension of the inherent topological structure within factorizable matrices remains limited. In this work, we reveal the topological properties of the linear mixture data, which allow for a remarkable reduction in the dimensionality of the NMF problem and reformulation of the NMF problem as an optimization problem with only K(K -1)variables, with K representing the number of pure components, irrespective of the initial data matrix dimensionality. This is achieved by uncovering the dual simplex structure of the data, with complementary simplex structures existing in both the features and samples spaces and leveraging the Sinkhorn transformation to uncover the relationship between these simplexes. We validate this approach in the context of an unconstrained general mixed images scenario and achieve a significant improvement in decomposition accuracy. Furthermore, we successfully apply the proposed approach in the biological context of bulk RNA-seq gene expression data unmixing and single-cell RNA-seq data clustering.

bioinformatics↗

bioRxiv2023

IL-15 priming alters IFN-γ regulation in murine NK cells

Natural killer (NK) effector functions can be triggered by inflammatory cytokines and engagement of activating receptors. NK cell production of IFN-{gamma}, an important immunoregulatory cytokine, exhibits activation-specific IFN-{gamma} regulation. Resting murine NK cells exhibit activation-specific metabolic requirements for IFN-{gamma} production, which are reversed for activating receptor-mediated stimulation following IL-15 priming. While both cytokine and activating receptor stimulation leads to similar IFN-{gamma} protein production, only cytokine stimulation upregulates Ifng transcript, suggesting that protein production is translationally regulated after receptor stimulation. Based on these differences in IFN-{gamma} regulation, we hypothesized that ex vivo IL-15 priming of murine NK cells allows a switch to IFN-{gamma} transcription upon activating receptor engagement. Transcriptional analysis of primed NK cells compared to naive cells or cells cultured with low-dose IL-15 demonstrated that primed cells strongly upregulated Ifng transcript following activating receptor stimulation. This was not due to chromatin accessibility changes in the Ifng locus or changes in ITAM signaling, but was associated with a distinct transcriptional signature induced by ITAM stimulation of primed compared to naive NK cells. Transcriptional analyses identified a common signature of c-Myc (Myc) targets associated with Ifng transcription. While Myc marked NK cells capable of Ifng transcription, Myc itself was not required for Ifng transcription using a genetic model of Myc deletion. This work highlights altered regulatory networks in IL-15 primed cells, resulting in distinct gene expression patterns and IFN-{gamma} regulation in response to activating receptor stimulation.

immunology↗

bioRxiv2023

ATG5 suppresses type I IFN-dependent neutrophil swarming and NETosis

Inflammation is critical for controlling infections, but when left unchecked can cause tissue damage and disease. For tuberculosis, the leading cause of death due to infection1, host inflammation is responsible for the clinical symptoms2, morbidity2, and mortality3,4. Specifically, neutrophil-dominated inflammation is associated with tuberculosis disease progression3,5,6. Therefore, understanding how neutrophil functions are regulated during infection is important for developing ways to prevent disease. Atg5 was the first gene shown to specifically function within neutrophils to promote control of Mycobacterium tuberculosis7, the causative agent of tuberculosis. ATG5 is best studied for its role in autophagy8-11, however, the protective activity of ATG5 in neutrophils was unexpectedly independent of other autophagy proteins and remained elusive7. We report here that ATG5, but not other autophagy proteins, is required in neutrophils to suppress neutrophil NETosis and swarming that occur due to elevated type I interferon levels during M. tuberculosis infection. The elevated level of NETosis that results from loss of ATG5 expression contributes to the early susceptibility of Atg5fl/fl-LysM-Cre mice during M. tuberculosis infection. NETosis is associated with poor disease outcomes in tuberculosis12,13 and COVID-19 patients14,15, as well as during other inflammatory diseases in humans16,17. Our studies identify an essential regulator of NETosis and elucidate previously unappreciated roles for ATG5 during infection, which may inform the design of host-directed therapeutics modulating these pathways.

immunology↗

bioRxiv2023

Costimulatory domains direct distinct fates of CAR-driven T cell dysfunction

Chimeric antigen receptor (CAR) engineered T cells often fail to enact effector functions after infusion into patients. Understanding the biological pathways that lead CAR T cells to failure is of critical importance in the design of more effective therapies. We developed and validated an in vitro model that drives T cell dysfunction through chronic CAR activation and interrogated how CAR costimulatory domains contribute to T cell failure. We found that dysfunctional CD28-based CARs targeting CD19 bear hallmarks of classical T cell exhaustion while dysfunctional 41BB-based CARs are phenotypically, transcriptionally and epigenetically distinct. We confirmed activation of this unique transcriptional program in CAR T cells that failed to control clinical disease. Further, we demonstrate that 41BB-dependent activation of the transcription factor FOXO3 is a significant contributor to this dysfunction and disruption of FOXO3 improves CAR T cell function. These findings identify that chronic activation of 41BB leads to novel state of T cell dysfunction that can be alleviated by genetic modification of FOXO3. SummaryChronic stimulation of CARs containing the 41BB costimulatory domain leads to a novel state of T cell dysfunction that is distinct from T cell exhaustion.

immunology↗

bioRxiv2022

Phantasus: web-application for visual and interactive gene expression analysis

Transcriptomic profiling became a standard approach to quantify a cell state, which led to accumulation of huge amount of public gene expression datasets. However, both reuse of these datasets or analysis of newly generated ones requires a significant technical expertise. Here we present Phantasus - a user-friendly web-application for interactive gene expression analysis which provide a streamlined access to more than 84000 public gene expression datasets, as well as allows analysis of user-uploaded datasets. Phantasus integrates an intuitive and highly interactive JavaScript-based heatmap interface with an ability to run sophisticated R-based analysis methods. Overall Phantasus allows to go all the way from loading, normalizing and filtering data to doing differential gene expression and downstream analysis. Phantasus can be accessed on-line at https://ctlab.itmo.ru/phantasus or https://artyomovlab.wustl.edu/phantasus or can be installed locally from Bioconductor (https://bioconductor.org/packages/phantasus). Phantasus source code is available at https://github.com/ctlab/phantasus under MIT licence.

bioinformatics↗

bioRxiv2021

Single-cell RNA transcriptome analysis reveals CXCL16/CXCR6 as maintenance factors for CNS tissue resident T cells that drive synapse elimination during viral recovery

BackgroundEmerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown. MethodsHere, we examined the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation, genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss. ResultsProfiling of host transcriptome at 25 days post-infection revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+ TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8+ T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 is required not only for the maintenance of WNV-specific, CD8 TRM cells in the post-infectious CNS, but also contributes to their expression of TRM cell markers. Moreover, CXCR6+CD8+ T cells are required for glial activation and ongoing synapse elimination. ConclusionsWe provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 during recovery may reduce CNS CD8+ TRM cells.

immunology↗

bioRxiv2021

Myeloid cell interferon responses correlate with clearance of SARS-CoV-2

The emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. While studies have reported immune profiling using single cell RNA sequencing in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. We performed longitudinal single-cell RNA sequencing of bronchoalveolar lavage (BAL) cell suspensions from adult rhesus macaques infected with SARS-CoV-2 (n=6) to delineate the early dynamics of immune cells changes. The bronchoalveolar compartment exhibited dynamic changes in transcriptional landscape 3 days post-SARS-CoV-2-infection (3dpi) (peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline). We observed the accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I IFN response was highly induced in the plasmacytoid dendritic cells. The presence of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin converting enzyme 2 (ACE2) expression was also observed. These macrophages were significantly recruited to the lungs of macaques at 3dpi and harbored SARS-CoV-2, while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery. The recruitment of a myeloid cell-mediated Type I IFN response is associated with the rapid clearance of SARS-CoV-2 infection in macaques.

immunology↗

bioRxiv2021

Lung epithelial signaling mediates early vaccine-induced CD4+ T cell activation and Mtb control

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (Mtb) infection is urgently needed. Early and superior Mtb control can be induced in M. bovis Bacillus Calmette-Guerin (BCG) vaccinated hosts when the innate immune response is targeted to generate effective vaccine-induced immunity. In the present study, we show that innate activation of DCs is critical for mucosal localization of clonally activated vaccine-induced CD4+ T cells in the lung, and superior early Mtb control. In addition, our study reveals that Th1/Th17 cytokine axis play an important role in superior vaccine induced immunity. Our studies also show that activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF{kappa}{beta}) pathway in lung epithelial cells is critical for the mucosal localization of activated vaccine-induced CD4+ T cells for rapid Mtb control. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control. ImportanceTuberculosis is a leading cause of death due to single infectious agent accounting 1.4 million deaths each year. The only licensed vaccine BCG is not effective due to variable efficacy. In our study, we determined the early immune events necessary for achieving complete protection in BCG vaccinated host. Our study reveals that innate activation of DCs can mediate superior and early Mtb control in BCG vaccinated host through lung epithelial cell signaling and localization of clonal activated, Mtb antigen specific, cytokine producing CD4+ T cells within the lung parenchyma and airways. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control.

immunology↗

bioRxiv2021

A homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

Interferon-lambda (IFN-{lambda}) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-{lambda} receptor (Ifnlr1), and is associated with IFN-{lambda} production by leukocytes. Strikingly, imaging of these homeostatic ISGs reveals localization to pockets of the epithelium and concentration in mature IECs. Correspondingly, a minority of mature IECs express these ISGs in public single-cell RNA sequencing datasets from mice and humans. Furthermore, we assessed the ability of orally-administered bacterial components to restore localized ISGs in mice lacking bacterial microbiota. Lastly, we find that IECs lacking Ifnlr1 are hyper-susceptible to initiation of murine rotavirus infection. These observations indicate that bacterial microbiota stimulate ISGs in localized regions of the intestinal epithelium at homeostasis, thereby preemptively activating antiviral defenses in vulnerable IECs to improve host defense against enteric viruses.

immunology↗

bioRxiv2020

A sustained type I IFN-neutrophil-IL-18 axis drives pathology during mucosal viral infection

Neutrophil responses against pathogens must be balanced between protection and immunopathology. Factors that determine these outcomes are not well-understood. In a mouse model of genital herpes simplex virus-2 (HSV-2) infection, which results in severe genital inflammation, antibody-mediated neutrophil depletion reduced disease. Comparative single cell RNA-sequencing analysis of vaginal cells against a model of genital HSV-1 infection, which results in mild inflammation, demonstrated sustained expression of interferon-stimulated genes (ISGs) only after HSV-2 infection primarily within the neutrophil population. Both therapeutic blockade of IFN/{beta} receptor 1 (IFNAR1) and genetic deletion of IFNAR1 in neutrophils concomitantly decreased HSV-2 genital disease severity and vaginal IL-18 levels. Therapeutic neutralization of IL-18 also diminished genital inflammation, indicating an important role for this cytokine in promoting neutrophil-dependent immunopathology. Our study reveals that sustained type I IFN signaling is a driver of pathogenic neutrophil responses, and identifies IL-18 as a novel component of disease during genital HSV-2 infection.

immunology↗

bioRxiv2020

Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model

Increasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain MHV-A59 (mCoV-A59) that recapitulated majority of clinical hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of {gamma}{delta} T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective {gamma}{delta} T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against COVID-19 in the elderly. Highlights - Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly. - Aged infected mice have systemic inflammation and inflammasome activation - Murine beta coronavirus (mCoV) infection results in loss of pulmonary {gamma}{delta} T cells. - Ketones protect aged mice from infection by reducing inflammation. eTOC BlurbElderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of {gamma}{delta} T cells that was corrected by ketogenic diet.

immunology↗

bioRxiv2020

Dysregulation of adipose ILC2 underlies thermogenic failure in aging

Aging impairs the integrated immunometabolic responses which have evolved to maintain core body temperature in homeotherms to survive cold-stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response but how adipose tissue-resident cells instigate thermogenic failure in aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2 are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2 during aging drive thermogenic failure. One Sentence SummaryAge-related changes in adipose tissue drive reprogramming of ILC2 that leads to impaired cold tolerance

immunology↗